Key proteins involved in insulin vesicle exocytosis and secretion

Abstract

Abstract.In vivo insulin secretion is predominantly affected by blood glucose concentration, blood concentration of amino acids, gastrointestinal hormones and free nerve functional status, in addition to other factors. Insulin is one of the most important hormones in the body, and its secretion is precisely controlled by nutrients, neurotransmitters and hormones. The insulin exocytosis process is similar to the neurotransmitter release mechanism. There are various types of proteins and lipids that participate in the insulin secretory vesicle fusion process, such as soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein, Ras-related proteins and vacuolar-type H + -ATPase (V-ATPase). Notably, the SNARE protein is the molecular basis of exocytotic activity. In the current review, the role of the vesicle membrane proteins (synaptobrevins, vesicle associated membrane proteins and target membrane proteins) and auxiliary proteins (Rab proteins and Munc-18 proteins) in vesicle fusion activity were summarized. A summary of these key proteins involved in insulin granule secretion will facilitate understanding of the pathogenesis of diabetes.

Removing the Gβγ-SNAP25 brake on exocytosis enhances insulin action, promotes adipocyte browning, and protects against diet-induced obesity

“…We took advantage of the βγ-SNAP25 interaction and its ability to serve as a brake on secretion to determine if limiting this physiologic inhibitory pathway could affect insulin secretion and/or weight gain in response to a high fat diet. Though SNAP25 is a well-known component of the insulin exocytosis machinery (13)(14)(15), we observed no alteration in GSIS from SNAP25 Δ3/Δ3 mice. However, adiposity and glucose homeostasis were markedly improved.…”

“…In order to test our hypothesis that removal of the Gβγ inhibition of SNAP25-mediated exocytosis would improve insulin secretion, we measured circulating glucose and insulin levels in SNAP25Δ3 mice during a glucose tolerance test (GTT). In our first study, 14 week-old, chow fed male mice (weighing 29.3±0.710 g vs. 28.9±0.749 g, SNAP25 +/+ vs. SNAP25 Δ3/Δ3 respectively, P = 0.695) received an IP injection of 2 mg/kg glucose.…”

“…The SNAP25 Δ3/Δ3 mouse has demonstrated the importance of the Gβγ-SNARE pathway in a number of neurological processes, including stress and pain processing, as well as long-term potentiation (6) and spatial memory (5). We hypothesized that the SNAP25 Δ3/Δ3 mouse may have an altered metabolic phenotype because neurological processes use SNAREdependent signals to regulate a number of metabolically important processes, such as feeding behavior, energy balance, and thermoregulation (7-12), and the secretion of important metabolic hormones, such as insulin (13)(14)(15).…”

“…The SNAP25 Δ3/Δ3 mouse has demonstrated the importance of the Gβγ-SNARE pathway in a number of neurological processes, including stress and pain processing, as well as long-term potentiation (6) and spatial memory (5). We hypothesized that the SNAP25 Δ3/Δ3 mouse may have an altered metabolic phenotype because neurological processes use SNAREdependent signals to regulate a number of metabolically important processes, such as feeding behavior, energy balance, and thermoregulation (7-12), and the secretion of important metabolic hormones, such as insulin (13)(14)(15).Metabolic diseases, such as diabetes and obesity, are estimated to have an annual global economic impact in the trillions of (US) dollars (16)(17)(18)(19)(20). The therapeutic value of the recently developed glutides and gliptins highlights the benefits of pharmacological agents that augment glucose stimulated insulin secretion (GSIS) (21).We hypothesized that the SNAP25Δ3 mutation would similarly enhance GSIS because previous studies have indicated that norepinephrine inhibits insulin exocytosis via the α2A adrenergic receptor (AR) through Gβγ inhibition of SNARE in the pancreatic β-cell (22).…”

A Pathway and Network Oriented Approach to Enlighten Molecular Mechanisms of Type 2 Diabetes Using Multiple Association Studies

“…Via controlling adipocyte survival, Focal adhesion kinases (FAK) regulate insulin 541sensitivity(Luk et al, 2017). SNARE protein contributes to fusion mechanism of insulin secretory 542 vesicles(Xiong et al, 2017). The study conducted by Boström et.…”